The long-term objective is to test the therapeutic potential of a category of macropolymers, those of linear conformation and molecular weights of the order of 10 to the sixth power or 10 to the seventh power daltons, against a variety of cardiovascular diseases. The addition of minute amounts of these macromolecules, called "drag-reducing polymers" (DRP) by hydrodynamicists, is known to double or even triple flow under a given pressure gradient (the so-called "Toms effect"). The phenomenon has been demonstrated also in blood flow through pipes with at least four different polymers. Three of these polymers, all of linear dimensions approaching 100 microns, double the rodent cardiac output. One polymer has been shown to dampen post-stenotic flow disturbances in the canine aorta and also to have a strong antiatherogenic effect in the rabbit aorta. Two of these polymers exert a potassium-sparing diuretic effect in the rat. The hemodynamic effects of DRPs would be examined in five experimental models: the pentobarbital-depressed heart, the heart with regional ischemia following coronary injection of glass microspheres, myocardial global ischemia caused by temporary ventricular fibrillation, myocardial regional ischemia and reperfusion following temporary ligation of the left anterior descending coronary artery, and irreversible hypotensive shock (severe hemorrhage followed by autotransfusion). After these exploratory experiments would have indicated which DRP is most effective "therapeutically" in which model, as assessed by hemodynamic criteria, a system would be chosen with a view of optimizing drug preparation and administration, defining the dose-response curves of single and multi-dose DRP injection, and examining other pharmacological features. Later the research would center on hemodynamic activities to elucidate the drug's mechanism of action. These experiments would involve studies on the effects of one or more DRPs on coronary blood flow, myocardial oxygen-consumption, blood volume and viscosity, and blood flow through the isolated limb.